This continuation of an established program emphasizes the techniques and concepts of cell and molecular biology, genetics, computational biology, musculoskeletal (limb) regenerative medicine and fundamental studies of immunology relevant to rheumatic, autoimmune and musculoskeletal diseases. Original population- based clinical research employs rigorous methodological design and statistical analysis. Support is requested for 6 postdoctoral trainees with an M.D., a Ph.D., or both, and for 1 predoctoral (Ph.D candidate) trainee. The faculty are carefully selected and perform research in areas of: I) Basic Biology including, 1) Adaptive Immunity (B and T Cell Biology), 2) Innate immunity, 3) Musculoskeletal (Limb) Regeneration and 4) Computational Biology, and II) Translational and Clinical Research including 1) Animal Models of Rheumatic and Musculoskeletal disorders, 2) Human Immunology and Genetics of Rheumatic Disease and 3) Patient-Centered Research in the Epidemiology and Outcomes of Rheumatic and Orthopedic Diseases. While the primary strength of the program resides in the direct and individual nature of the interaction in the laboratory between each trainee and the responsible faculty member(s), substantial didactic experiences, the medical school and university environments, along with a series of structured activities foster interactions and supplement training. Trainees audit semester courses at Harvard Medical School in their field of basic science, while population science investigators obtain an MPH or a similar degree at the Harvard School of Public Health. Postdoctoral trainees in a combined clinical and research training program join this program after completing their clinical training. Graduate students join the program only after completing course work and are in Harvard Ph.D Programs in Biomedical and Biological Sciences including (1) Immunology and 2) Bioinformatics and Integrative Genomics. The program is hosted in the Division of Rheumatology, Immunology and Allergy at Brigham and Women?s Hospital. Importantly, approximately 40% of faculty are part of the program but located in other divisions, departments and Harvard Medical School affiliated Institutions and are selected for their relevance to the program goals and their outstanding scientific and training expertise. Besides Brigham and Women?s Hospital Departments of Medicine, Orthopedics and Neurology, they include faculty at 1) the Broad Institute of Harvard and MIT, 2) Boston Children?s Hospital, 3) Massachusetts General Hospital, 4) Harvard Medical School Departments of Immunology, Biomedical Informatics, and Genetics, 5) Harvard University Department of Stem Cell and Regenerative medicine, and 6) the Harvard School of Public Health. The program goal is to provide an ongoing pipeline of highly trained and expert investigators prepared for and focused in rheumatic and related musculoskeletal disease research.